tbuckley/cabot-search huggingface dataset:
Abstract P674: Associations Between Visceral Adipose Tissue Area and Density With Renal Artery Calcification
Authors: Harsimran Bajwa, Matthew A Allison, Michael Criqui, Joao A Ac Lima, Jingzhong Ding, Siddique A Abbasi, Ron Blankstein, Isac C Thomas
Journal: Circulation (2023)

Introduction: Visceral adipose tissue (VAT) has been associated with higher levels of atherosclerosis. Renal artery calcification (RAC) secondary to atherosclerosis has been found to be associated with hypertension and an increase in all-cause mortality. Hypothesis: There are significant associations between VAT area and density with the presence and extent of renal artery calcification. Methods: Within the Multi-Ethnic Study of Atherosclerosis (MESA) abdominal aortic calcification ancillary study, 1,978 participants from five of the six field centers around the US underwent abdominal CT imaging to measure VAT and RAC. Standardized questionnaires were used to obtain demographic and health history data. Blood samples were assayed for lipid, glucose, creatinine, and adipokine levels. Rate ratio regression was used to estimate prevalence ratios (PRs) for the presence of RAC, while linear regression was used to estimate linear coefficients for the severity of RAC among participants with RAC &gt; 0. Results: Of the 1,978 participants, 1,196 participants had complete visceral adiposity and renal artery measurements. After controlling for sociodemographic variables, CVD risk factors, adipokine levels, and VAT density, VAT area was not associated with RAC presence (PR 1.02, 95% CI 0.89, 1.16, p = 0.80), while greater VAT density was borderline protective for RAC presence (PR 0.89, 95% CI 0.78, 1.02, p = 0.10) when controlling for the same factors and VAT area. 354 participants had RAC &gt; 0 and were included in linear regression analyses assessing RAC severity. After controlling for sociodemographic variables, CVD risk factors, adipokine levels, and VAT density, VAT area was significantly associated with RAC severity (slope 63.32, 95% CI 11.84, 114.81, p = 0.02), while VAT density was not associated with RAC severity (slope 9.78, 95% CI -40.87, 60.44, p = 0.71). Conclusions: In this relatively large, multi-ethnic cohort of adults from five communities in the US, we have demonstrated that higher density VAT may be protective for RAC presence, while greater VAT area is significantly associated with RAC severity. While this is the first study examining the relationship between VAT and RAC, our results are consistent with previous studies describing associations between increased VAT area and decreased VAT density with outcomes including hypertension, hypercholesterolemia, and metabolic syndrome. Category: Subclinical Cardiovascular Disease
Abstract MP64: Impact of a Vegan Diet Compared to Omnivorous Diet on Blood Lipids and Weight Among Identical Twins: The Twins Nutrition Study (TwiNS) Randomized Controlled Trial
Authors: Matthew J Landry, Catherine P Ward, Christopher D Gardner
Journal: Circulation (2023)

Introduction: Vegan diets, where animal- and all their by-products are excluded from the diet, have gained popularity. Growing evidence suggests potential cardiovascular benefits of vegan diets due to improvements in diet quality (i.e., higher consumption of vegetables, fruits whole grains, nuts, legumes, and seeds). Methods: The TwiNS randomized controlled trial examined the cardiometabolic impact of a healthy vegan diet compared to a healthy omnivorous diet (NCT05297825). These diets were examined in 22 pairs of identical twins, where one twin followed the vegan diet, and the other twin followed the omnivorous diet for 8 weeks. Diet specific meals were provided via a meal delivery service from baseline through week 4, and during weeks 5-8 participants prepared their own diet appropriate meals and snacks. The primary outcome was difference in LDL cholesterol from baseline to week 8. Secondary outcome measures included change in triglycerides, HDL-cholesterol and body weight. Adherence to study diets, ease/difficulty in following the diets, participant energy levels, and sense of wellbeing were also measured. A linear mixed model was used to investigate a difference in the change in primary and secondary outcomes from baseline and included a random effect for twin pair, to account for the correlation between identical twins. Results: Participants were generally healthy adults, average age 39.6 years, primarily non-Hispanic White, and had an average BMI of 26.2. On average, twins randomized to the healthy vegan diet had decreased their LDL-cholesterol more after 8 weeks compared to twins on the healthy omnivorous diet (-15.2 vs. -2.3mg/dL, 95% CI: 4.3-24.8). Participants on the healthy vegan diet also had decreased their body weight more after 8 weeks (-1.9 vs. -0.29 kg, 95% CI: 0.9-3.0). No significant differences were observed between the vegan and omnivorous diets for secondary outcomes of triglycerides or HDL-C. Conclusion: This study contributes to growing evidence that vegan diets may offer a protective cardiometabolic advantage compared to a healthy, omnivorous diet. Further analyses of the TwINS trial will examine changes to the gut microbiome (i.e., microbial diversity), inflammatory markers, and other health factors.
Abstract MP78: Race/Ethnic Disparities in Children’s Cardiovascular Health: The Role of Social Disadvantage in Early Life
Authors: Liliana Aguayo, Nicole D Fields
Journal: Circulation (2023)

Introduction: The loss of cardiovascular health (CVH) begins early in life and disproportionately affects racial/ethnic minorities, particularly children in single parent households, and households with lower education, family income and food insecurity. However, the contribution of these social determinants to CVH disparities in childhood are poorly understood. Hypothesis: We hypothesized that racial/ethnic differences in CVH among US children are explained by social disadvantages. Methods: Data from the 2013-2018 National Health and Nutrition Examination Survey for children aged 2-18 (N=4,792) were used. CVH was measured using the AHA Life’s Essential 8 scores that combine nicotine exposure, diet, physical activity, sleep, body mass index, and blood pressure, lipids, and glucose. Oaxaca-Blinder decomposition methods were used to quantify the contributions of parental education, marital status and household income to poverty ratio, and food security to differences in CVH by race and sex. Results: Mean CVH score was highest among non-Hispanic White (mean [SE] = 73.7 [0.5]) than non-Hispanic Black (71.3 [0.6]) and Hispanic children (71.0 [0.4]). There was no significant difference among Black-White boys (mean differences [MD] = -1.52; 95% CI: -3.25, 0.21). Black girls had significantly lower CVH than White girls (MD= -2.66; 95% CI: -4.40, -0.91). Differences in parental college education accounted for 46% of the differences in CVH scores (MD = -1.21; 95% CI: -1.89, -0.54). Among Hispanic children, both boys (MD = -2.47; 95% CI: -4.22, -0.73) and girls (MD = -3.09; 95% CI: -4.60, -1.58) had significantly lower CVH scores than White boys and girls, respectively. Differences in parental education explained 66% of the difference in CVH among White-Hispanic boys and girls (MD= -0.66; 95%CI-1.11, -0.20; and MD= -0.66; 95%CI-1.20, -0.13). Discussion: Differences in parental college education largely explained lower levels of CVH among US Black and Hispanic children, a predictor of future cardiovascular disease.
Abstract MP26: Lifestyle, Genetic and Epigenetic Factors Associated With Serum Glyca Levels and Results From a Lifestyle Intervention Trial on This Cardiovascular Risk Biomarker
Authors: Oscar Coltell, Jose Sorli, Rebeca Fernandez-Carrion, Dolores Corella
Journal: Circulation (2023)

Introduction: GlycA is a novel biomarker of systemic inflammation and cardiovasculardisease (CVD) risk. It is measured by a signal in the proton nuclear magnetic resonance(NMR) spectra (from the N-acetyl methyl groups of N-acetylglucosamine residues).Epidemiological studies have reported associations between GlycA and increased CVD risk.However, there are few investigations examining the link between GlycA levels and lifestylefactors (diet, physical activity (PA), sleep, etc.), gut microbiota, or genetics at the genome-wide level (GWAS); and even fewer studies have analyzed serum GlycA and genome-widemethylation (EWAS) or the effect of lifestyle intervention on the reduction of GlycA.Therefore, our aims were: i) to investigate lifestyle, genetic, and epigenetic factorsassociated with serum GlycA; ii) to examine changes in serum GlycA after 1-y lifestyleintervention in a Mediterranean population. Methods: Cross-sectional and lifestyleintervention analyses were undertaken in a Mediterranean population at highcardiovascular risk (n=426 older subjects with metabolic syndrome in the PREDIMED-Plus-Valencia trial; ISRCTN89898870). Lifestyle variables were assessed by validatedquestionnaire and quantile-g-computation methods were used to analyze their jointcontribution. Serum GlycA was measured by NMR spectroscopy. Genome-wide genotypingand DNA-methylation were determined by Illumina arrays (OmniExpress and EPIC).Exploratory omics-wide and targeted analyses on GlycA (focusing on autophagy genes andmicrobiome-host-related genes) were undertaken. Changes in serum GlycA levels after a 1-y lifestyle intervention (intensive intervention group with Mediterranean diet and PA versusthe control group) were assessed in a subset of participants. Results: GlycA levels atbaseline (Mean: 1.49+/-0.20 mmol/L) were significantly associated with branched-chainamino acids and a highly atherogenic lipid profile. Also, we obtained an association withdietary factors and PA. Omics analysis suggested novel SNPs (in SFMBT2- DAB1 and TEK)and methylation sites (CpG in RAD50, PPP1R9B, ZDHHC4 and LSP1) associated with GlycA. We also obtained associations with host-microbiome related SNPs in FUT2 and withmethylation signals in selected autophagy genes (STX7, TAX1BP1, ATG9B and ATG10).Moreover, in the intervention trial we detected a significant (P&lt;0.05) decrease in the GlycAlevels after 1 y of intensive lifestyle intervention in comparison with the control group. Conclusions: Serum GlycA levels were strongly associated with cardiometabolic risk factorsin this Mediterranean population and linked to lifestyle variables. Additionally, we haveidentified some genetic and epigenetic factors related to GlycA that may modulate theselevels.
Abstract P453: Apolipoprotein B, Low-Density Lipoprotein Particle Number, Non-High-Denisity Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Total Cholesterol for Atherosclerotic Cardiovascular Disease Risk Prediction in Young Adults
Authors: John T Wilkins, Hongyan Ning, Konrad Sawicki, Konrad T Sawicki, Allan D Sniderman, James D Otvos, Jamal S Rana, Venkatesh Murthy, Venkatesh L Murthy, Ravi V Shah, Norrina B Allen, Donald Lloyd-Jones
Journal: Circulation (2023)

Introduction: Measures of atherogenic particle number (apoB and LDL particle number [LDL-P]) are stronger predictors of atherosclerotic cardiovascular disease (ASCVD) risk than measures of cholesterol concentration (LDL-C, non-HDL-C, total cholesterol [TC]) in middle-aged adults. It is unclear if this is true for younger adults. Methods: Among CARDIA participants (ppts), NMR was used to measure apoB and LDL-P. Non-HDL-C and TC were measured using standard assays; LDL-C was calculated using the Friedewald equation. We stratified the ppts into two age windows: age 20-30y (n=1645) and age 30-40y (n=2922). We used adjusted Cox proportional hazards models to assess the associations of 1SD higher apoB, LDL-P, non-HDL-C, LDL-C, or TC with incident ASCVD events. We substituted each measure of atherogenic lipid burden for TC in a modified Pooled Cohort Equation (PCE) model (with and without HDL-C); and model performance (discrimination and reclassification) was evaluated. Results: There were 81 and 163 ASCVD events over (median [IQR]) 31.8y (31.1-32.0y) for the age 20-30 age window and over 26.8y (19.1-27.1y) for the 30-40y age window, respectively. In ppts age 20-30y, a 1SD higher apoB, LDL-P, non-HDL-C, and LDL-C were significantly associated with incident ASCVD in demographic adjusted models. The strengths of associations with ASCVD were not significantly different across these measures. For the 30-40y age window, all measures of atherogenic lipoproteins were significantly associated with ASCVD; the strengths of association were not significantly different across atherogenic lipid measures in all models. There were no significant differences in the C-statistic and no improvement in reclassification when each measure was used to replace TC in the PCE model. Conclusions: ApoB, LDL-P, LDL-C or non-HDL-C may be slightly better markers of long-term ASCVD risk than TC in adults &lt; 30y. However, in adults between 30-40y all measures of atherogenic lipid burden appeared to be equivalent predictors of long-term risk.
Abstract P322: Transcriptomic Analysis of Severe Obesity Identifies Novel Genes in Hispanic/Latino Populations With a High Burden of Disease
Authors: Priya Sharma, Hung-Hsin Chen, Wanying Zhu, Hannah G. Polikowsky, Peter Mccormick, Kalypso Karastergiou, Susan Fried, Anne E Justice, Miryoung Lee, Mariaelisa Graff, Yasser Mohammad, Joesph Mccormick, Susan P Fisher-hoch, Kari E North, Jennifer Below
Journal: Circulation (2023)

The US prevalence of severe obesity [(SevO), body mass index [BMI] ≥40 kg/m 2 )] is increasing at an alarming rate; women and Hispanic Latino populations have experienced among the greatest increases. While genome-wide association studies (GWAS) have identified &gt;1000 loci associated with body mass index, the function of much of this variation is unknown. Gene expression measures can ] link genetic variation and disease highlighting pathways for targeted therapeutic intervention, but to-date, few studies have examined the role of gene expression to identify molecular signatures associated with SevO. To this end, we leveraged extant whole blood (WB) RNA sequencing (RNAseq) data in 75 SevO cases and 116 controls (with BMI = 18-25) collected from randomly selected Mexican Americans in the Cameron County Hispanic Cohort (CCHC) to identify patterns associated with SevO. We used established protocols and alignment, yielding 18,565 genes after quality control. We applied DESeq2 to assess DE associated with SevO, using a negative binomial regression model with a gene-specific dispersion parameter, adjusted for sex, age, T2D, hypertension, hypercholesterolemia, and 10 probabilistic estimation of expression residual (PEER) factors. After FDR correction, 124 genes were significantly DE, including top genes C1RL , IL4R, and RGS16 . We identified several replications of the 124 genes in a transcriptomic follow-up study of 52 SevO cases and 59 normal weight controls- 20 genes displayed directionally consistent and FDR significant evidence of replication. We additionally identified several replications of the 124 genes in subcutaneous adipose tissue (SAT) from 19 NYC community volunteers, including for RGS16 , C1RL , and IL4R. 2- sample MR assessed causal associations between SevO and gene dysregulation, using SevO GWAS from DIAMANTE and CCHC eQTLs. Upregulated IL4R demonstrate pleiotropy, among other genes (e.g., REM2, ENGASE, and SCAP ). Collectively, these data demonstrate how transcriptomic studies may elevate understanding of SevO and inform efforts to reduce health disparities associated with SevO in HL populations.
Abstract P194: Proteomic Profiling of Pulmonary Function Decline and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yura Lee, Christine Ladd-Acosta, Alanna C Morrison, Kari E North, Eric Boerwinkle, Amil M Shah, Stephanie J London, Bing Yu
Journal: Circulation (2023)

Introduction: Measures of pulmonary function are associated with cardiovascular disease risk; however, the underlying mechanism remains unclear. Hypothesis: We hypothesize that protein biomarkers are associated with pulmonary function decline, as well as the risk of subsequent incident coronary heart disease (CHD), heart failure (HF), and mortality. Methods: We included participants from the Atherosclerosis Risk in Communities (ARIC) study with plasma proteome measured by SOMAscan and spirometric measures (forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC)) at both visits 2 (1990-1992) and 5 (2011-2013). Cross-sectional associations of protein levels with FEV1 and FVC at both visits were assessed using multivariable linear regression. The decline of FEV1 was evaluated among proteins related to cross-sectional FEV1 and FVC measures. The FEV1-decline-related proteins were further probed into the effects on incident CHD, HF, and mortality, using Cox proportional hazard models post-visit 2. Results: Out of 4,677 proteins, 364 were cross-sectionally associated with both FEV1 and FVC at visit 2 (n=11,354, age 57, 23% blacks, and 56% women) and 5 (n=3,517, age 75, 17% blacks, and 58% women) at FDR &lt;0.05. Twenty-seven of 364 proteins were associated with FEV1 decline between visits (FDR &lt;0.05). The protein effects were more predominant in women than men (p &lt;0.001). Among 27 FEV1 decline-related proteins, 25 and 27 were associated with incident HF and mortality during an average of 29 years follow-up (FDR &lt;0.05, Figure ). Gamma-aminobutyric acid receptor-associated protein showed the greatest effect with FEV1 decline, and its per SD increase was associated with 20% higher risk of HF and mortality. Compared to HF and mortality, FEV1 decline-related proteins were less associated with incident CHD. Conclusions: Twenty-seven proteins related to pulmonary function decline were heavily associated with the risk of HF and mortality, suggesting shared etiology between those conditions.
Abstract MP48: Cross-Sectional and Prospective Associations Between Slow-Wave Sleep and Type 2 Diabetes: The Multi-Ethnic Study of Atherosclerosis
Authors: Sina Kianersi, Susan Redline, Morgana Mongraw-Chaffin, Tianyi Huang
Journal: Circulation (2023)

Introduction: Slow-wave sleep (also known as stage N3 sleep), a marker of deep restorative sleep, is implicated in the regulation of insulin resistance and glucose homeostasis and may impact cardiometabolic health. Hypothesis: We conducted both cross-sectional and prospective analyses to test the hypothesis that higher proportion and longer duration of N3 sleep are associated with reduced diabetes risk in older adults. Methods: A sub-sample of participants from the Multi-Ethnic Study of Atherosclerosis completed one-night polysomnography at Exam 5 (2010-2013) and were prospectively followed until Exam 6 (2016-2018). Continuous measures of N3 proportion (%) and duration (minutes) and their corresponding quartiles were used as primary exposures. Diabetes status was assessed in both Exams and was defined as fasting blood glucose≥126 mg/dl, HbA1c≥6.5%, antidiabetic medications use, or self-reported doctor diagnosis of diabetes. We used Modified Poisson regression to examine the cross-sectional associations of N3 proportion and duration with prevalent diabetes in Exam 5. Cox proportional hazards models were used to estimate risk of incident diabetes according to N3 measures. We sequentially adjusted for sociodemographic factors, lifestyles, adiposity measures, and multiple sleep-related factors, such as average sleep duration, apnea-hypopnea index, and insomnia symptoms. Results: In cross-sectional analyses (N=2,026, mean age: 69 years), diabetes prevalence was 28% (n=572). Compared to participants in the first quartile of N3 proportion (&lt;2.0%), participants in the fourth quartile (≥15.4%) were 29% less likely to have prevalent diabetes (Prevalence ratio: 0.71; 95% CI: 0.58,0.87; P -trend: 0.0016]. The association was attenuated and not significant after adjusting for confounders, particularly BMI. In prospective analyses (N=1,251), there were 129 incident diabetes cases over 6,346 person-years of follow-up (mean follow-up time: 5.1 years). A curvilinear relationship was observed between N3 proportion and incident diabetes risk. The hazard ratio (95% CI) of developing diabetes versus the lowest quartile was 0.45 (0.25,0.81) for quartile 2, 0.31 (0.14,0.70) for quartile 3, and 0.30 (0.10,0.90) for quartile 4 ( P -nonlinearity=0.0169, based on restricted cubic spline model). The association remained significant in the fully adjusted model ( P -nonlinearity=0.0319). The results were similar for N3 duration. Conclusions: Higher N3 proportion and longer N3 duration were prospectively associated with lower diabetes risk in a nonlinear fashion among older American adults.
Abstract P318: Life’s Essential 8 as a Measure of Cardiovascular Health in the Women’s Health Initiative (WHI)
Authors: Eugenia Wong, Sara Jones, Nora Franceschini, Matthew A Allison, Lorena Garcia, Sherrie Wise Thomas, Aladdin H Shadyab, Wayne D Rosamond
Journal: Circulation (2023)

Introduction: In 2022, the American Heart Association (AHA) introduced Life’s Essential 8 (LE8) as an updated definition of cardiovascular health (CVH). Sleep health was added to the original Life’s Simple 7 (LS7), and a new scoring system was developed. We evaluated how LE8 characterizes CVH among women in the WHI. Hypothesis: We hypothesized that the average LE8 score would be moderate, with only a small group of WHI participants having high CVH. Methods: The WHI recruited 161,808 post-menopausal women from 40 clinical centers in 1993-1998. This analysis included 116,514 women without self-reported CVD, with measured height, weight, and blood pressure, and self-reported smoking history, sleep duration, physical activity, diet, diabetes, and cholesterol at baseline. CVH components were scored from 0-100 based on participants’ achievement of each health factor or behavior. Scores were assigned per AHA guidance with some adaptations made based on data availability. Lacking measured values, glucose and lipid scores were calculated based on history and treatment status of diabetes and high cholesterol. Overall LE8 scores were calculated as the unweighted mean of all components. Scores were further categorized into high (80-100), moderate (50-79), or low (0-49), with higher scores indicating positive CVH. Results: The average LE8 score among WHI participants at baseline was 71.5 (standard deviation (SD): 12.5; range 20.6-100) ( Figure ). Overall, sleep scores were high (mean: 86.5, SD 19.1). The lowest scores were found in diet (mean: 39.5, SD 31.3) and physical activity (mean: 47.7, SD: 43.5). LE8 classified 28.1% of WHI participants (32,773/116,514) as having high CVH whereas a prior analysis of LS7 found that 17.7% and 6.1% had ideal levels of 5 and 6-7 CVH components, respectively. Conclusions: Based on the new LE8 definition, most women had moderate CVH at study baseline, with approximately a quarter having high CVH. Although sleep health was high, scores for other health behaviors demonstrated considerable room for improvement.